Background: The immunogenicity of seasonal trivalent influenza vaccine (TIV) in solid organ transplant (SOT) recipients remains suboptimal. We hypothesized that analysis of pre-vaccination T- and B- cell associated cytokine profiles may be useful in predicting which patients are more likely to develop protective vaccine response.

Methods: We performed a subanalysis of a clinical trial aimed at comparing the safety and immunogenicity of high-dose intradermal (ID) versus intramuscular (IM) TIV in SOT recipients. All patients were analyzed as a single group. Levels of selected cytokines known to be important in B and T cell responses to viral antigens were measured pre- and post-vaccination (interferon [IFN]-γ, interleukin [IL]-2, IL-4, IL-5, IL-6, IL-12 and IL-21, and tumour necrosis factor [TNF]-α) (median interval between sampling: 34 days) using a Luminex® technology-based multiplexed immunoassay. We compared cytokine profiles according to vaccine response, defined as seroconversion (≥4-fold increase in hemagglutination inhibition [HAI] antibody titers) to ≥1 influenza vaccine antigen.

Results: Paired pre- and post-vaccination samples were analyzed for 155 patients (including 84 and 71 patients receiving the ID and IM vaccines, respectively). Pre-vaccination IL-6 levels were significantly higher in patients achieving vaccine response (median: 0.51 vs. 0.32 pg/mL; P-value = 0.021). After adjusting for clinical and immunosuppression-related variables, pre-vaccination serum IL-6 levels remained predictive of vaccine response (OR per unitary increment: 1.71; 95% confidence interval: 1.21-2.42; P-value = 0.002). Pre-vaccination IL-6 levels also showed a significant positive correlation with post-vaccination HAI antibody titers against the A/H1N1 strain (Spearman's rho: 0.256; P-value = 0.001). Vaccination was associated with significant increases in IL-4 and TNF-α (p<0.0001 for both), as well as a decrease in IL-5 (p=0.0007). Nevertheless, there were no significant differences between vaccine responders and non-responders in absolute changes or coefficient variations of post-vaccination cytokine levels compared to baseline values. No cytokine differences were seen by vaccine type (ID vs IM).

Conclusions: Baseline serum IL-6 levels, a cytokine critically involved in the terminal differentiation of B-cells into plasma cells, act as an independent predictor of vaccine response in SOT recipients.

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